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Abstract Rabbit meat is tender, high in protein, low in fat and cholesterol, and offers several nutritional benefits. However, it has a stronger taste and can be challenging to cook. The global rabbit industry has been developing steadily, and China's total rabbit meat production has exceeded half of the world's total production in 2021. Along with the progress of the production process, the meat of the nutrition and taste at the same time, to improve smell also can get better control, solved the problems met in rabbit meat production. This article discusses the attributes of rabbit meat and outlines the deodorization, texture adjustment, and water retention techniques currently used in rabbit meat processing, aiming to offer a theoretical foundation for the advancement of rabbit meat processing technology.

Abstract The freshness of aquatic products is directly related to the safety and health of the people. Traditional methods of detecting the freshness of Conger myriaster rely on manual operations, which are labor‐intensive, inefficient, and highly subjective. This paper combines computer vision and the DWG‐YOLOv8 network model to establish an intelligent classification method for C. myriaster freshness. Through image augmentation, 484 C. myriaster samples were expanded to 2904 samples. The YOLOv8n model was improved by simplifying the network backbone, introducing Ghost convolution and the new DW‐GhostConv, thereby reducing the number of parameters and computational load. Test results show that the recognition accuracy of the DWG‐YOLOv8 model reached 98.958%, outperforming models such as ResNet18, Mobilenetv3 small, and Swin transformer v2 tiny. The model's parameter count is 16.609 K, the inference time is 57.80 ms, and the model size is only 102 KB. The research provides a reliable method for online intelligent and nondestructive detection of C. myriaster freshness.

Abstract Quorum sensing (QS) inhibition has emerged as a promising target for directed drug design, providing an appealing strategy for developing antimicrobials, particularly against infections caused by drug‐resistant pathogens. In this study, we designed and synthesized a total of 33 β‐nitrostyrene derivatives using 1‐nitro‐2‐phenylethane (NPe) as the lead compound, to target the facultative anaerobic bacterial pathogen Serratia marcescens. The QS‐inhibitory effects of these compounds were evaluated using S. marcescens NJ01 and the reporter strain Chromobacterium violaceum CV026. Among the 33 new β‐nitrostyrene derivatives, (E)‐1‐methyl‐4‐(2‐nitrovinyl)benzene (m‐NPe, compound 28) was proven to be a potent inhibitor that reduced biofilm formation of S. marcescens NJ01 by 79%. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) results revealed that treatment with m‐NPe (50 μg/ml) not only enhanced the susceptibility of the formed biofilms but also disrupted the architecture of biofilms by 84%. m‐NPe (50 μg/ml) decreased virulence factors in S. marcescens NJ01, reducing the activity of protease, prodigiosin, and extracellular polysaccharide (EPS) by 36%, 72%, and 52%, respectively. In S. marcescens 4547, the activities of hemolysin and EPS were reduced by 28% and 40%, respectively, outperforming the positive control, vanillic acid (VAN). The study also found that the expression levels of QS‐ and biofilm‐related genes (flhD, fimA, fimC, sodB, bsmB, pigA, pigC, and shlA) were downregulated by 1.21‐ to 2.32‐fold. Molecular dynamics analysis showed that m‐NPe could bind stably to SmaR, RhlI, RhlR, LasR, and CviR proteins in a 0.1 M sodium chloride solution. Importantly, a microscale thermophoresis (MST) test revealed that SmaR could be a target protein for the screening of a quorum sensing inhibitor (QSI) against S. marcescens. Overall, this study highlights the efficacy of m‐NPe in suppressing the virulence factors of S. marcescens, identifying it as a new potential QSI and antibiofilm agent capable of restoring or improving antimicrobial drug sensitivity.

Abstract Fault recorded data has been proven to be effective for fault diagnosis of overhead transmission lines. Utilizing deep learning to mine potential fault patterns in fault recording data is an inevitable trend. However, it is usually difficult to obtain massive labeled fault recording data, which results in deep learning‐based fault diagnosis models not being adequately trained. Although data augmentation methods provide ideas for expanding the training data, existing data augmentation algorithms (e.g. random perturbation‐based augmentation) may lead to distortion of multi‐view data, that is, time domain data and frequency domain data of the fault recorded data, which results in the inconsistency of physical properties and statistical distributions of the generated data and the actual recording data, and misguides the training of the models. Hence, this study proposes a transmission line fault classification method via the multi‐view synergistic enhancement of fault recording data. The methodology proposes to start with a synergistic enhancement of multi‐view data such as time and frequency domains of fault recording data, and utilizes contrastive learning to further improve the performance of the fault classification model while ensuring that the generated data is not distorted. Experimental results on three real‐world datasets validate the effectiveness of the proposed method.

Abstract Background Coronavirus disease 2019 (COVID‐19) vaccination in patients with rheumatic disease is of practical clinical importance. This study aimed to perform a comprehensive bibliometric analysis of COVID‐19 vaccination in patients with rheumatic disease and indicate possible directions for future studies. Methods Research articles and reviews related to COVID‐19 vaccinations in patients with rheumatic diseases were retrieved from Science Citation Index Expanded of the Web of Science Core Collection. The CiteSpace and VOSviewer software were used to depict network mapping showing the collaborations among countries, institutions, and authors. Current hotspots and future directions were derived by analyzing highly cited/co‐cited documents and keywords. Results In total, 615 documents published in 194 academic journals, including 505 articles and 110 reviews contributed by 5068 authors from 1693 institutions in 79 countries/regions, were finally included and analyzed. The United States and the University of London were the most productive country and cooperative institution, respectively. Author analysis showed that cooperation between different authors was largely confined to only several groups. Vaccines and Journal of the American Academy of Dermatology were the journals with the most publications and citations per document, respectively. Cluster analysis showed that the keywords can be categorized into groups like kidney disease, antibody response, COVID‐19 vaccine, vaccination, validation, safety, and giant cell arteritis. Conclusions The efficacy and safety of COVID‐19 vaccination in patients with rheumatic disease are being continuously investigated. Future studies on COVID‐19 vaccination in patients with rheumatic diseases could focus on antibody response, validation, and vaccine safety.

Abstract Outlet short circuit on the low‐voltage (LV) side and winding inter‐turn short circuit faults are hazardous to transformer operation. To investigate the formation mechanism of winding insulation faults of distribution transformer, ANSYS Maxwell was used to build a coupled magnetic field‐circuit model with the same structural dimension as the actual distribution transformer. An outlet short circuit and winding inter‐turn insulation faults were set by using the voltage‐controlled switch in the external circuit of the model. Subsequently, the differences in the electromagnetic characteristics and the electrodynamic force distributions of the windings under three operating conditions, namely, nominal load, three‐phase outlet short circuit on the LV side and inter‐turn insulation failure were studied, respectively. The results show that compared with the rated load, in the cases of outlet short circuit and inter‐turn insulation faults, the amplitude of winding current increases by 20 and 50 times, the magnetic field strength grows by 20 and 17 times, and the electrodynamic force rises by 400 and 230 times, respectively. Outlet short circuit fault is more likely to cause the winding instability and deformation, and inter‐turn short circuit fault can easily burn out winding insulation. Therefore, corresponding preventive measures were proposed.

Abstract To scavenge energy from imperceptible vibrations, this paper investigates the broadband response and output performance of a microvibrational piezoelectric energy harvesting system with mechanical stopper. The energy harvesting system comprises a cantilever beam made of piezoelectric material, which is affixed with a coil at its unbound end and a mechanical stopper. The coil is placed in a magnetic field to provide an ultra‐low level excitation. The electromechanical model is derived according to force integration method (FIM) and Hertz's contact theory, and numerical simulations are undertaken to evaluate the influence of the excitation level, and the gap on the performance. For the linear counterpart without stopper, experimental results indicate the system generates a peak power of 24.12 μW with matched resistance under excitation with a level of 0.003 N and a frequency of 200.3 Hz. When a polydimethylsiloxane (PDMS) stopper is introduced, the vibration of the piezoelectric beam exhibits an obvious nonlinearity with an amplitude of micron scale. Increasing the excitation level and decreasing the gap could efficiently broaden the response bandwidth. Experimental results demonstrate that a copper stopper with larger elastic modulus results in a wider response frequency range, and the half‐power bandwidth could reach 37.1 Hz under excitation with a level of 0.003 N.

Abstract Reactive jammers select jamming strategies according to the users’ responses; thus, conventional anti‐jamming methods such as frequency hopping are inadequate to defeat the jamming attack. In this article, the authors propose a novel uncoupled deception scheme to trap the reactive jammer into attacking a decoy channel in distributed networks. Specifically, the authors design a multi‐functional network utility for every user to mislead the jammer with a minimum energy consumption while achieving the highest network throughput. Based on the network utility, the anti‐jamming problem is formulated as an exact potential game such that the existence of Nash equilibrium can be guaranteed theoretically. The authors further propose a back‐to‐back coordination‐based learning algorithm to reach the optimal channel selection and power adaption in a non‐cooperative way. To alleviate the lack of mutual information exchange, the back‐to‐back coordination mechanism derives all users to deceive the jammer by inferring others’ strategies based on a shared belief. Simulation results show that the proposed algorithm yields higher network throughput and efficiency‐cost ratio compared to the state‐of‐the‐art cooperative schemes.

Abstract The increased penetration of renewable energy sources and the intensification of peak‐valley differences present challenges to peak regulation in the power system. Fulfilling the peak regulation needs of the power system solely through generation‐side resources proves to be challenging. Large‐scale fixed frequency air‐conditioning (FFAC) and inverter air‐conditioning (IAC) are high‐quality flexible load resources. This paper proposes a hierarchical coordinated control strategy of air‐conditioning (AC) loads for peak regulation service. In the first layer of the control strategy, the load aggregator collaborates with multiple AC groups to ensure the completion of peak regulation tasks with specific power‐constrained requirements. In the second layer of the control strategy, the control centre of each group optimizes the temperature adjustment values for each AC load, aiming to reduce incentive costs. Finally, the proposed method is validated through simulations, demonstrating its capability to achieve coordinated control of FFAC and IAC loads under various power‐constrained requirements. Furthermore, the simulation demonstrates the effectiveness of the control strategy in reducing user discomfort and the AC's incentive costs.

Abstract Cyber–physical distribution systems with renewable energy should have high resilience under extreme conditions. However, in a distribution system with deep cyber–physical coupling, the propagation of information risk impairs the resilience of the system. This paper proposes a strategy to improve the resilience of cyber–physical distribution systems that considers cross‐space propagation of information risk. First, the mechanism for interaction between the cyber space and physical space is analyzed, and an information risk cross‐space propagation model is proposed. Second, the risk status of key device nodes is quantified according to the risk propagation model, and an optimization strategy for information risk control is obtained, whose objective function is the minimum risk of the coupling network. Third, a fault restoration strategy that considers cyber space risk is proposed. Finally, the paper reports experiments using the modified IEEE 33‐node and 123‐node distribution networks to simulate the proposed strategy and verify its effectiveness.

Societal Impact Statement Conventional pest management measures release large amounts of chemical or plastic pollutants into the environment. Nicotiana benthamiana, a commonly employed laboratory model plant, demonstrated remarkable lethality and attractiveness towards several important Hemiptera and Thysanoptera insect pests. Field trials showed that the N. benthamiana plants can be used as a dead‐end trap to successfully control these pests, comparable to commercial plastic sticky traps. Notably, the N. benthamiana in the field grew well without negatively impacting crop growth, natural enemies, and pollinators. This study unearths a new benefit of N. benthamiana and develops an easy‐to‐apply and sustainable strategy for field pest control. Summary Hemiptera and Thysanoptera insects pose persistent threats to agricultural production. Conventional management strategies involve the release of chemical or plastic agents, causing adverse environmental and global health issues. Notably, Nicotiana benthamiana, a globally utilized model plant, exhibits remarkable lethal effects and attraction towards these pests. In this study, we explored the potential of using N. benthamiana for Hemiptera and Thysanoptera pest control in the laboratory and field. Through net cover and three field assays over 2 years, we demonstrated the efficacy and benefits of using N. benthamiana as a field‐deployed pest control dead‐end trap. N. benthamiana demonstrated nearly 100% lethality to whiteflies, aphids, and thrips, with emitted volatiles attracting these insects. Field trials showed that potted and planted N. benthamiana blocks and traps whiteflies and thrips from several Solanaceae and Cucurbitaceae crops effectively, comparable to common commercial yellow and blue sticky boards. Moreover, N. benthamiana in the field exhibited robust growth in commercial greenhouses without negatively impacting crop growth, natural enemies, and pollinators. Our study introduces an innovative, easily implementable, and sustainable approach for controlling Hemiptera and Thysanoptera pests. Moreover, it unveils the novel utility of N. benthamiana in field‐based pest management.

Abstract Higher serum cholesterol levels have been associated with an increased risk of dry eye disease (DED). The relationship between statin (HMG‐CoA reductase inhibitor) use and DED in patients with hyperlipidemia remains unclear. To investigate the association between statin use and the risk of DED in patients with hyperlipidemia, we conducted a population‐based retrospective cohort study utilizing data from Taiwan's Longitudinal Generation Tracking Database. Patients were categorized into statin users and nonusers, with a 5‐year follow‐up period. The study identified patients with newly diagnosed hyperlipidemia, excluding those with prior DED diagnoses. Matching and adjustments for covariates resulted in 41,931 individuals in each group. Patients receiving statin therapy were compared with those unexposed. Cumulative exposure doses were also evaluated to assess dose–response relationships. The primary outcome was the incidence of DED diagnosed during the follow‐up period. Cox proportional hazards regression models estimated the risk of DED, and conditional logistic regression analyzed the dose–response effect of statin exposure. Among 41,931 matched pairs, statin users exhibited a slightly increased risk of developing DED compared with nonusers (adjusted hazard ratio, 1.06; 95% CI, 1.02–1.11; p

Abstract The ruminal microbiota generates biogenic methane in ruminants. However, the role of host genetics in modifying ruminal microbiota‐mediated methane emissions remains mysterious, which has severely hindered the emission control of this notorious greenhouse gas. Here, we uncover the host genetic basis of rumen microorganisms by genome‐ and transcriptome‐wide association studies with matched genome, rumen transcriptome, and microbiome data from a cohort of 574 Holstein cattle. Heritability estimation revealed that approximately 70% of microbial taxa had significant heritability, but only 43 genetic variants with significant association with 22 microbial taxa were identified through a genome‐wide association study (GWAS). In contrast, the transcriptome‐wide association study (TWAS) of rumen microbiota detected 28,260 significant gene–microbe associations, involving 210 taxa and 4652 unique genes. On average, host genetic factors explained approximately 28% of the microbial abundance variance, while rumen gene expression explained 43%. In addition, we highlighted that TWAS exhibits a strong advantage in detecting gene expression and phenotypic trait associations in direct effector organs. For methanogenic archaea, only one significant signal was detected by GWAS, whereas the TWAS obtained 1703 significant associated host genes. By combining multiple correlation analyses based on these host TWAS genes, rumen microbiota, and volatile fatty acids, we observed that substrate hydrogen metabolism is an essential factor linking host–microbe interactions in methanogenesis. Overall, these findings provide valuable guidelines for mitigating methane emissions through genetic regulation and microbial management strategies in ruminants.

Abstract Intron retention (IR) constitutes a less explored form of alternative splicing, wherein introns are retained within mature mRNA transcripts. This investigation demonstrates that the cell division cycle (CDC)‐like kinase 2 (CLK2) undergoes liquid–liquid phase separation (LLPS) within nuclear speckles in response to heat shock (HS). The formation of CLK2 condensates depends on the intrinsically disordered region (IDR) located within the N‐terminal amino acids 1‐148. Phosphorylation at residue T343 sustains CLK2 kinase activity and promotes overall autophosphorylation, which inhibits the LLPS activity of the IDR. These CLK2 condensates initiate the reorganization of nuclear speckles, transforming them into larger, rounded structures. Moreover, these condensates facilitate the recruitment of splicing factors into these compartments, restricting their access to mRNA for intron splicing and promoting the IR. The retained introns lead to the sequestration of transcripts within the nucleus. These findings extend to the realm of glioma stem cells (GSCs), where a physiological state mirroring HS stress inhibits T343 autophosphorylation, thereby inducing the formation of CLK2 condensates and subsequent IR. Notably, expressing the CLK2 condensates hampers the maintenance of GSCs. In conclusion, this research unveils a mechanism by which IR is propelled by CLK2 condensates, shedding light on its role in coping with cellular stress.

Abstract The lymph node is the most common site of distant metastasis of cervical squamous cell carcinoma (CSCC), which elicits dismal prognosis and limited efficiency for treatment. Elucidation of the mechanisms underlying CSCC lymphatic metastasis would provide potential therapeutic strategies for nodal metastatic of CSCC. Here, based on in vivo lymphatic metastasis screening model, a circular RNA is identified that is termed as lymph node metastasis associated circRNA (LNMAC), is markedly upregulated in lymphatic metastatic CSCC and correlated with lymph node metastasis. Overexpression of LNMAC dramatically augments the metastatic capability of CSCC cells to the lymph node via inducing lymphangiogenesis. Mechanistically, LNMAC epigenetically upregulates fibroblast growth factor 2 (FGF2) expression by directly associating with histone acacetylase 1 (HDAC1), preventing Importin α6/8‐mediated nuclear translocation of HDAC1 and eliciting histone H3K27ac‐induced FGF2 transcriptional activation. Treatment with 3F12E7, an anti‐FGF2 monoclonal antibody, effectively inhibits LNMAC‐induced CSCC lymphatic metastasis. Taken together, these findings indicate that LNMAC plays a crucial role in FGF2‐mediated lymphangiogenesis and lymphatic metastasis, highlighting that LNMAC might be a therapeutic target for lymph node metastasis in CSCC patients.

Abstract Mortality rates due to lung cancer are high worldwide. Although PD‐1 and PD‐L1 immune checkpoint inhibitors boost the survival of patients with non‐small‐cell lung cancer (NSCLC), resistance often arises. The Warburg Effect, which causes lactate build‐up and potential lysine‐lactylation (Kla), links immune dysfunction to tumor metabolism. The role of non‐histone Kla in tumor immune microenvironment and immunotherapy remains to be clarified. Here, global lactylome profiling and metabolomic analyses of samples from patients with NSCLC is conducted. By combining multi‐omics analysis with in vitro and in vivo validation, that intracellular lactate promotes extracellular lipolysis through lactyl‐APOC2 is revealed. Mechanistically, lactate enhances APOC2 lactylation at K70, stabilizing it and resulting in FFA release, regulatory T cell accumulation, immunotherapy resistance, and metastasis. Moreover, the anti‐APOC2K70‐lac antibody that sensitized anti‐PD‐1 therapy in vivo is developed. This findings highlight the potential of anti lactyl‐APOC2‐K70 approach as a new combination therapy for sensitizing immunotherapeutic responses.

Abstract Dual‐mode readout platforms with colorimetric and electrochemiluminescence (ECL) signal enhancement are proposed for the ultrasensitive and flexible detection of the monkeypox virus (MPXV) in different scenes. A new nanotag, Ru@U6‐Ru/Pt NPs is constructed for dual‐mode platforms by integrating double‐layered ECL luminophores and the nanozyme using Zr‐MOF (UiO‐66‐NH2) as the carrier, which not only generates enhanced ECL and colorimetric signals but also provide greater stability than that of commonly used nanotags. Dual‐mode platforms are used within 15 min from the “sample in” to the “result out” steps, without nucleic acid amplification. The colorimetric mode allows the screening of MPXV with the visual limit of detection (vLOD) of 0.1 pM (6 × 108 copies µL−1) and the ECL mode supports quantitative detection of MPXV with an LOD as low as 10 aM (6 copies·µL−1), resulting in a broad sensing range of 60 to 3 × 1011 copies·µL−1 (10 orders of magnitude). Validation is conducted using 50 clinical samples, which is 100% concordant to those of quantitative polymerase chain reaction (qPCR), indicating that Ru@U6‐Ru/Pt NPs‐based dual‐mode sensing platforms showed great promise as rapid, sensitive, and accurate tools for diagnosis of the nucleic acid of MPXV and other infectious pathogens.

Abstract 1D grain boundaries in transition metal dichalcogenides (TMDs) are ideal for investigating the collective electron behavior in confined systems. However, clear identification of atomic structures at the grain boundaries, as well as precise characterization of the electronic ground states, have largely been elusive. Here, direct evidence for the confined electronic states and the charge density modulations at mirror twin boundaries (MTBs) of monolayer NbSe2, a representative charge‐density‐wave (CDW) metal, is provided. The scanning tunneling microscopy (STM) measurements, accompanied by the first‐principles calculations, reveal that there are two types of MTBs in monolayer NbSe2, both of which exhibit band bending effect and 1D boundary states. Moreover, the intrinsic CDW signatures of monolayer NbSe2 are dramatically suppressed as approaching an isolated MTB but can be either enhanced or suppressed in the MTB‐constituted confined wedges. Such a phenomenon can be well explained by the MTB‐CDW interference interactions. The results reveal the underlying physics of the confined electrons at MTBs of CDW metals, paving the way for the grain boundary engineering of the functionality.

Abstract The link between mantle plumes and the formation of large igneous provinces (LIPs) is well established although the anatomy of these remains equivocal. Recent experimental studies and geophysical data suggest that the mantle plume head is more likely to be irregular and asymmetric, rather than an axisymmetric flattened disk. The Emeishan large igneous province (ELIP) provides a unique opportunity to test this hypothesis. According to robust petrographic, geochronologic, and geochemical evidence from the late Permian basalts in the Sichuan Basin, and in conjunction with a comprehensive compilation of geologic maps and published geochemical data from the ELIP, we identified several giant radial “fingering” structures. Based on the shallow mantle source from the center to margin in the ELIP and relief of the lithosphere‐asthenosphere boundary, we propose a new mantle plume model to explain the evolution of the Emeishan plume periphery, where narrow finger‐like protrusions and plumelets developed outwards from the main body of the plume to the edges of the flattened plume head. Dragged fingers might have been torn apart into some plumelets, which dispersed and were trapped beneath the thinnest lithosphere relief, and eventually erupted to form small‐scale flood basalt in the Outer Zone of the ELIP.

Abstract Exploring the molecular packing and interaction between chiral molecules, no matter single enantiomer or racemates, is important for recognition and resolution of chiral drugs. However, sensitive and non‐destructive analysis methods are lacking. Herein, an intermolecular‐charge transfer (ICT) based spectroscopy is reported to reveal the differences in interaction between the achiral acceptor 1,2,4,5‐tetracyanobenzene (TCNB) and the chiral donors, including S, R, and racemic naproxen (S/R/rac‐NAP). In this process, S‐NAP+TCNB and R‐NAP+TCNB display a narrower band gap attributed to the newly formed ICT state. In contrast, the mixed rac‐NAP and TCNB exhibit almost no significant change due to the strong affinity between the stereoisomers according to the Wallach's rule. Thus, S/R‐NAP can be easily distinguished from rac‐NAP based on significantly different optical behavior. The single crystal analysis, infrared spectroscopy, fluorescence spectroscopy, and theoretical calculation of naproxen confirm the importance of carboxyl for this differentiation in molecular packing and interaction. In addition, the esterification derivatization of naproxen achieves the manipulation of the intermolecular interaction model of racemates from the absolute Wallach's rule to a coexisting form of Wallach's rule and ICT. Further, visualized chiral purification of naproxen by the simple cocrystallization method is achieved through the collaboration of ICT and Wallach's rule.

Abstract Exploring effective antibacterial approaches for targeted treatment of pathogenic bacterial infections with reduced drug resistance is of great significance. Combinational treatment modality that leverages different therapeutic components can improve the overall effectiveness and minimize adverse effects, thus displaying considerable potential against bacterial infections. Herein, red blood cell membrane fuses with macrophage membrane to develop hybrid cell membrane shell, which further camouflages around drug‐loaded liposome to fabricate biomimetic liposome (AB@LRM) for precise antibacterial therapy. Specifically, photoactive agent black phosphorus quantum dots (BPQDs) and classical antibiotics amikacin (AM) are loaded in AB@LRM to accurately target the inflammatory sites through the guidance of macrophage membrane and long residence capability of red blood cell membrane, eventually exerting efficacious antibacterial activities. Besides, due to the excellent photothermal and photodynamic properties, BPQDs act as an efficient antibacterial agent when exposed to near‐infrared laser irradiation, dramatically increasing the sensitivity of bacteria to antibiotics. Consequently, the synergistic sterilizing effect produced by AB@LRM further restricts bacterial resistance. Upon laser irradiation, AB@LRM shows superior anti‐inflammatory and antibacterial properties in models of P. aeruginosa‐infected pneumonia and wounds. Hence, this light‐activatable antibacterial nanoplatform with good biocompatibility presents great potential to advance the clinical development in the treatment of bacterial infections.

Abstract Clinical trials of Chimeric Antigen Receptor T‐cell (CAR‐T) therapy have demonstrated remarkable success in treating both solid tumors and hematological malignancies. Nanobodies (Nbs) have emerged as promising antigen‐targeting domains for CARs, owing to their high specificity, robust stability, and strong affinity, leading to significant advancements in the field of Nb‐CAR‐T. In the realm of T‐cell acute lymphoblastic leukemia (T‐ALL) targets, CD5 stands out as a potentially excellent candidate for T‐cell‐based CAR therapy, due to its distinct expression on the surface of malignant T‐ALL cells. To mitigate graft‐versus‐host disease associated with allogeneic CAR‐T, γδT cells are selected and stimulated from peripheral blood mononuclear cells, and γδT cells are engineered via CRISPR/Cas9 to eliminate fratricide, enabling the creation of fratricide‐resistant CAR‐γδTCD5− cells. In vitro transcribed (IVT) mRNA is used to construct CAR‐T, presenting a safer, faster, and cost‐effective method compared to traditional viral vector approaches. In this study, a CD5‐VHH library is constructed, and specific CD5‐nanobodies are screened for subsequent use in CD5‐CAR‐γδTCD5− therapy. IVT‐mRNA‐CD5‐CAR‐γδTCD5− cells exhibited favorable functional characteristics and demonstrated antitumor efficacy against malignant T cell lines, underlining the potential for advancing mRNA‐CD5‐CAR‐γδTCD5− therapy.

Background Poor cardiovascular‐kidney‐metabolic (CKM) health is associated with premature mortality and excess morbidity in the United States. Adverse social conditions have a prominent impact on cardiometabolic diseases during the life course. We aim to examine the association between social risk profile (SRP) and CKM multimorbidity among US adults. Methods and Results We used data from the National Health and Nutrition Examination Survey from 1999 to 2018. The definition of CKM syndrome is the coexistence of subclinical or clinical cardiovascular disease, chronic kidney disease, and metabolic disorders. We classified participants by 4 CKM stages according to the different clinical severity of different forms of CKM syndrome. We calculated the summed number of positive SRP measures, including employed, high‐income level, food secure, high education attainment, private insurance, owning a house, and married, as SRP scores and classified them into 4 levels by quartiles: low (0–2), lower‐middle (3–4), upper‐middle (5–6), and high (7–8). A total of 18 373 US adults, aged 20 to 79 years, were included in our analyses. There were 2567 (9.4%) participants with low SRP score level. Most individual SRP measures and a combined SRP score were associated with CKM stages. Compared with high SRP score level, low SRP level was associated with higher odds of having CKM stage 1 (odds ratio [OR], 1.34 [95% CI, 1.06–1.70]), CKM stage 2 (OR, 2.03 [95% CI, 1.59–2.58]), CKM stage 3 (OR, 5.28 [95% CI, 3.29–8.47]), and CKM stage 4 (OR, 5.97 [95% CI, 4.20–8.49]). Conclusions Cumulative social disadvantage, denoted by higher SRP burden, was associated with higher odds of CKM multimorbidity, independent of demographic and lifestyle factors.

Background Serum lipids are causally involved in the occurrence of atherosclerosis, but their roles in cerebral small vessel disease remain unclear. This study aimed to investigate the causal roles of lipid or apolipoprotein traits in cerebral small vessel disease and to determine the effects of lipid‐lowering interventions on this disease. Methods and Results Data on genetic instruments of lipids/apolipoproteins, as well as characteristic cerebral small vessel disease manifestations, including small vessel stroke (SVS) and white matter hyperintensity (WMH), were obtained from publicly genome‐wide association studies. Through 2‐sample Mendelian randomization analyses, it was found that decreased levels of high‐density lipoprotein cholesterol (odds ratio [OR], 0.85, P=0.007) and apolipoprotein A‐I (OR, 0.83, P=0.005), as well as increased level of triglycerides (OR, 1.16, P=0.025) were associated with a higher risk of SVS. A low level of high‐density lipoprotein cholesterol (OR, 0.93, P=0.032) was associated with larger WMH volume. Specifically, the genetically determined expressions of lipid fractions in various size‐defined lipoprotein particles were more closely related to the risk of SVS than WMH. Moreover, it was found that the hypertension trait ranked at the top in mediating the causal effect of hyperlipidemia on SVS and WMH by using Mendelian randomization‐based mediation analysis. For drug‐target Mendelian randomization, the low‐density lipoprotein cholesterol‐reducing genetic variation alleles at HMGCR and NL1CL1 genes and the high‐density lipoprotein cholesterol‐raising genetic variation alleles at the CETP gene were predicted to decrease the risk of SVS. Conclusions The present Mendelian randomization study indicates that genetically determined hyperlipidemia is closely associated with a higher risk of cerebral small vessel disease, especially SVS. Lipid‐lowering drugs could be potentially considered for the therapies and preventions of SVS rather than WMH.

Background Stroke is a leading cause of death worldwide, with a lack of effective treatments for improving the prognosis. The aim of the present study was to identify novel therapeutic targets for functional outcome after ischemic stroke . Methods and Results Cis‐expression quantitative trait loci data for druggable genes were used as instrumental variables. The primary outcome was the modified Rankin Scale score at 3 months after ischemic stroke, evaluated as a dichotomous variable (3–6 versus 0–2) and also as an ordinal variable. Drug target Mendelian randomization, Steiger filtering analysis, and colocalization analysis were performed. Additionally, phenome‐wide Mendelian randomization analysis was performed to identify the safety of the drug target genes at the genetic level. Among >2600 druggable genes, genetically predicted expression of 16 genes (ABCC2, ATRAID, BLK, CD93, CHST13, NR1H3, NRBP1, PI3, RIPK4, SEMG1, SLC22A4, SLC22A5, SLCO3A1, TEK, TLR4, and WNT10B) demonstrated the causal associations with ordinal modified Rankin Scale (P

Abstract Patients with breast tumours that metastasise to the brain have limited treatment options and a very poor prognosis. More effective therapeutic strategies are desperately needed for this patient population. Recent evidence demonstrates that brain metastases arising from breast tumours display altered energy production that results in enhanced autophagy. Preclinical studies have shown that genetically or pharmacologically disrupting the autophagy pathway significantly decreases the brain metastatic burden, resulting in improved animal survival and increased sensitivity to lapatinib. These findings pave the way for the development of novel strategies targeting autophagy for breast cancer patients with brain metastatic disease.

Abstract Background Non‐small‐cell lung cancer (NSCLC) often presents at later stages, typically associated with poor prognosis. Autophagy genes play a role in the progression of tumors. This study investigated the clinical relevance, prognostic value, and biological significance of RBBP4 in NSCLC. Methods We assessed RBBP4 expression using the GSE30219 and TCGA NSCLC datasets and NSCLC cells, exploring its links with clinical outcomes, tumor immunity, and autophagy genes through bioinformatics analysis after transcriptome sequencing of RBBP4‐knockdown and control PC9 cells. We identified differentially expressed genes (DEGs) and conducted Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and protein–protein interaction network analyses. The significance of autophagy‐related DEGs was evaluated for diagnosis and prognosis using the GSE30219 dataset. Experiments both in vivo and in vitro explored the biological mechanisms behind RBBP4‐mediated autophagic cell death in NSCLC. Results RBBP4 overexpression in NSCLC correlates with a poorer prognosis. Eighteen types of immune cell were significantly enriched in cultures that had low RBBP4 expression compared high expression. DEGs associated with RBBP4 are enriched in autophagy pathways. Transcriptomic profiling of the PC9 cell line identified autophagy‐related DEGs associated with RBBP4 that exhibited differential expression in NSCLC, suggesting prognostic applications. In vitro experiments demonstrated that RBBP4 knockdown induced autophagy and apoptosis in PC9 cells, promoting cell death, which was inhibited by 3‐MA. In vivo, targeted siRNA against RBBP4 significantly reduced tumor development in PC9 cell‐injected nude mice, elevating autophagy‐related protein levels and inducing apoptosis and necrosis in tumor tissues. Conclusion In NSCLC, RBBP4 upregulation correlates with poor prognosis and altered immunity. Its knockdown induces autophagic cell death in NSCLC cells. These results indicate RBBP4 as a potential NSCLC diagnostic marker and its autophagy modulation as a prospective therapeutic target.

Abstract Myeloperoxidase (MPO) is the most specific marker of the myeloid lineage, essential for diagnosing acute myeloid leukemia and mixed phenotype acute leukemia with myeloid components. In this regard, we present a unique case of B‐acute lymphoblastic leukemia (B‐ALL) with isolated MPO expression in bone marrow blasts detected by flow cytometry and immunohistochemistry, while peripheral blood blasts were negative for MPO expression. In this report, our discussion encompasses diagnostic pitfalls from a laboratory testing perspective in similar cases and includes a literature review. Furthermore, we emphasize the necessity of conducting a comprehensive analysis for the accurate diagnosis of MPO‐positive B‐ALL cases.

Abstract Nucleophosmin 1 (NPM1) mutations occur in approximately one‐third cases of adult de novo acute myeloid leukemia (AML). Identification of NPM1 mutations is important for classification, risk stratification, tailored therapy, and monitoring minimal residual disease. Mutational analysis is widely used for detecting NPM1 mutations. Immunochemistry assessing abnormal cytoplasmic localization of NPM1 protein has been used as a surrogate marker for NPM1 mutations. We present a case of AML with mutated NPM1 that was missed by sequencing analysis but detected by immunohistochemistry. This case highlights the value of immunohistochemistry in identifying NPM1 mutations in a subset of AML cases.

Abstract Aircraft coating process has been an important part in manufacturing process of modern aviation products. For coating defect detection, the manual observation with naked eyes is usually utilized, which leads to low production efficiency. In this paper, the authors propose the improved YOLOv5‐OBB with the channel‐spatial attention block (CSAB), feature pyramid non‐local module (FPNM) and structured sparsity slimming criterion (SSSC). The CSAB can pay more attention to effective channel information features from the channel dimension and the target information area from the spatial dimension. The effective non‐local module called FPNM is proposed to further improve the detection accuracy. The authors utilize the oriented bounding boxes (OBB) to reduce redundant background information for coating defect detection. In addition, the SSSC is proposed to achieve network slimming and trade‐off between the efficiency and accuracy. The experimental results on several datasets demonstrate the effectiveness of the authors’ scheme, which achieves superior performance.

Abstract Presurgical evaluation is still challenging for MRI‐negative epilepsy patients. As non‐invasive modalities are the easiest acceptable and economic methods in determining the epileptogenic zone, we analyzed the localization value of common non‐invasive methods in MRI‐negative epilepsy patients. In this study, we included epilepsy patients undergoing presurgical evaluation with presurgical negative MRI. MRI post‐processing was performed using a Morphometric Analysis Program (MAP) on T1‐weighted volumetric MRI. The relationship between MAP, magnetoencephalography (MEG), scalp electroencephalogram (EEG), and seizure outcomes was analyzed to figure out the localization value of different non‐invasive methods. Eighty‐six patients were included in this study. Complete resection of the MAP‐positive regions or the MEG‐positive regions was positively associated with seizure freedom (p = 0.028 and 0.007, respectively). When an area is co‐localized by MAP and MEG, the resection of the area was significantly associated with seizure freedom (p = 0.006). However, neither the EEG lateralization nor the EEG localization showed statistical association with the surgical outcome (p = 0.683 and 0.505, respectively). In conclusion, scalp EEG had a limited role in presurgical localization and predicting seizure outcome, combining MAP and MEG results can significantly improve the localization of epileptogenic lesions and have a positive association with seizure‐free outcome. Plain Language Summary Due to the lack of obvious structure abnormalities on neuroimaging examinations, the identification of epilepsy lesions in MRI‐negative epilepsy patients can be difficult. In this study, we intended to use non‐invasive examinations to explore the potential epileptic lesions in MRI‐negative epilepsy patients and to determine the results accuracy by comparing the neuroimaging results with the epilepsy surgery outcomes. A total of 86 epilepsy patients without obvious structure lesions on MRI were included, and we found that the combinations of different non‐invasive examinations and neuroimaging post‐processing methods are significantly associated with the seizure freedom results of epilepsy surgery.

Abstract Aims The combination of haemoglobin, albumin, lymphocytes, and platelets (HALP) is a new metric used to assess patient prognosis in many diseases. This study aimed to assess the relationship between HALP and short‐ and long‐term mortality in patients with heart failure. Methods and results This retrospective cohort study included adult patients with heart failure who were hospitalized between 2019 and 2021. The primary outcomes were 1‐month mortality and 1‐year mortality. The multivariable logistic regression analysis was used to evaluate the association between HALP and the risk of mortality. Stratified analyses were conducted based on New York Heart Association functional classification (NYHA) stage (II/III, IV) and left ventricular ejection fraction (LVEF,

Abstract Liver cancer is the most prevalent fatal malignancy across the globe. The present study aims to explore the molecular mechanism of E3 ligase WWP1 in liver cancer cell proliferation and invasion/migration. RT‐qPCR and Western blot were performed to detect WWP1, KLF14, and VEPH1 expressions in liver cancer cell lines. Furthermore, WWP1 expression was silenced in cells, followed by the detection of cell viability, proliferation, and invasion/migration by CCK‐8, colony formation, and Transwell assays, respectively. ChIP was used to analyze the binding relationship between WWP1 and KLF14. We measured the KLF14 ubiquitination level and KLF14 enrichment on the VEPH1 promoter after MG132 treatment. Dual‐luciferase reporter assay was used to validate the binding relationship between KLF14 and VEPH1. Consequently, WWP1 was highly expressed in liver cancer cells; WWP1 silencing reduced the proliferation and invasion/migration of liver cancer cells. Mechanistically, WWP1 promoted KLF14 ubiquitination degradation; KLF14 was enriched on the VEPH1 promoter to promote its transcription and protein expression. Inhibiting KLF14 or VEPH1 partially minimized the inhibitory effect of WWP1 silencing on liver cancer cell proliferation and invasion/migration. In summary, WWP1 degrades KLF14 through ubiquitination, hence repressing VEPH1 expression and accelerating proliferation and invasion/migration of liver cancer cells.

Abstract The fluctuation and intermittency of wind and solar power outputs result in increased regulation pressure on thermal units in power systems. Adjustable energy‐intensive loads (such as electrolytic aluminium and steel plants) have great potential for participating in demand response (DR) programs with the goal of reducing thermal unit regulation pressure. This paper proposes an optimal scheduling method of unit commitment (UC) which gives consideration to energy‐intensive loads participating in wind and solar power consumption. The UC method adopts the nonparametric kernel density estimation method to model wind and solar power outputs and then uses the Frank‐Copula function to describe the correlation between the scenarios of wind and solar power outputs. A stochastic unit commitment (SUC) model introduces a chance‐constrained theory of a reserve coefficient to describe time‐variant scenarios on the basis of the deviation between the typical and simulative scenarios. The simulation results based on the IEEE 118‐bus system show that the energy‐intensive load in the SUC model can flexibly adjust and respond to changes in wind and solar power output, reduce the impact of the uncertainties of wind and solar power output, and promote the consumption of wind and solar power.

Abstract In this paper, an optimal distributed guidance law is proposed for cooperatively intercepting a manoeuvering target in three dimensional (3D) framework. Based on the 3D kinematic model of interceptors and the target, the kinematic engagement equations in line‐of‐sight (LOS) coordinate can be obtained. Along the LOS direction, a finite‐time consensus based on directed communication topology is applied to guarantee arrival‐time coordination of multiple interceptors, and sliding mode control is adopted to compensate target manoeuver. In the plane perpendicular to LOS, optimal control is used to design guidance law such that closed‐loop LOS angular rates converge to a tunable small neighbourhood of zero. The proposed cooperative guidance law is proved in theory, and its effectiveness is verified by simulations.

Abstract Diabetic retinopathy (DR), the main cause of irreversible blindness, is one of the most common complications of diabetes. At present, deep convolutional neural networks have achieved promising performance in automatic DR detection tasks. The convolution operation of methods is a local cross‐correlation operation, whose receptive field determines the size of the local neighbourhood for processing. However, for retinal fundus photographs, there is not only the local information but also long‐distance dependence between the lesion features (e.g. hemorrhages and exudates) scattered throughout the whole image. The proposed method incorporates correlations between long‐range patches into the deep learning framework to improve DR detection. Patch‐wise relationships are used to enhance the local patch features since lesions of DR usually appear as plaques. The Long‐Range unit in the proposed network with a residual structure can be flexibly embedded into other trained networks. Extensive experimental results demonstrate that the proposed approach can achieve higher accuracy than existing state‐of‐the‐art models on Messidor and EyePACS datasets.

Abstract At present, data obtained from the Global Positioning System (GPS) is significantly valuable in mobility research. However, GPS‐based data lacks include trip purpose information. Consequently, many researchers have endeavoured to predict or impute these missing attributes. Existing studies have focused on constructing more features to improve prediction accuracy, but paid less attention to the model's applicability and transferability. In this study, five trip purposes are extracted, including education, recreation, personal, shopping, and transportation, from Chengdu Household Travel Survey (HTS) data. The individual and trip characteristics that are common and can be easily derived from GPS data are carefully selected and extracted. Point of Interest (POI) data of the trip destination are also collected to enhance input characteristics. To obtain more accurate results, an ensemble learning model, Gradient Boosting Decision Trees (GBDT), is employed to predict trip purposes. grid search and cross‐validation techniques are used to optimize the hyper‐parameters. Empirical results show that the proposed model achieves 0.788 accuracy, which is 22.17%, 14.53%, 10.36%, and 6.77% higher than Multinominal Logit (MNL), Artificial Neural Network (ANN), Random Forest (RF), and Deep Belief Network (DBN), respectively. It is also found that although increasing trip features improve the model's accuracy, it simultaneously impairs model's transferability and generalizability.

Abstract The present study aimed to evaluate the efficacy of long‐term riociguat sequentially combined with balloon pulmonary angioplasty (BPA) for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Eight inoperable CTEPH patients were enrolled in this study, who have been administrated riociguat 2.5 mg three times daily for about 8 years, then underwent several sessions of BPA procedures. Data are prospectively collected to evaluate clinical outcomes, hemodynamics, exercise capacity, and right heart size and function by echocardiography at baseline, 8 years after riociguat, and 3 months after the final BPA. Eight patients (mean age 54.9 ± 11.4 years) were treated with riociguat 2.5 mg three times daily for 95.0 ± 10.7 months. Cardiac index (CI) (1.5 ± 0.5 L/min/m2 to 2.4 ± 0.6 L/min/m2, p = 0.005), 6 min walking distance (6MWD) (329.6 ± 87.5 m to 418.1 ± 75.8 m, p = 0.016), and pulmonary vascular resistance (PVR) (1336.9 ± 320.2 dyn·s·cm−5 to 815.4 ± 195.6 dyn·s·cm−5, p = 0.008) were significant improvement after riociguat treatment. Mean 4.1 ± 1.6 additional combinational BPA sessions and mean 18.8 ± 8.1 balloon dilations were performed. Mean pulmonary artery pressure (54.1 ± 11.1 mmHg to 33.6 ± 7.7 mmHg, p = 0.002) and PVR (815.4 ± 195.6 dyn·s·cm−5 to 428.3 ± 151.2 dyn·s·cm−5, p＜0.001) were further decreased. CI (2.4 ± 0.6 L/min/m2 to 2.7 ± 0.7 L/min/m2, p = 0.028) and 6MWD (418.1 ± 75.8 m to 455.7 ± 100.0 m, p = 0.038) were increased significantly. After long‐term riociguat treatment, sequential combination with BPA delivered considerably incremental benefits on exercise capacity and pulmonary hemodynamics, as well as right heart size and function of technically inoperable CTEPH patients.

Abstract Objective To evaluate the predictive value of echo features of radial probe endobronchial ultrasound (RP‐EBUS) in the differential diagnosis of malignant and benign 1esions. Methods The clinical data of 336 patients with peripheral pulmonary lesions (PPLs) undergoing RP‐EBUS were analyzed in order to evaluate the predictive value of the three EBUS echo features including continuous margin, absence of a linear‐discrete air bronchogram, and heterogeneous in pulmonary lesions. The sensitivity and specificity for each echoic feature or in combination in diagnosing malignancy or benignity were determined. Results 336 cases of PPLs including 216 cases of malignant lesions and 120 cases of benign lesions. The sensitivity and specificity of the continuous margin to the diagnosis of malignant lesions were 86.11% and 17.50%. The sensitivity and specificity of the absence of a linear‐discrete air bronchogram to the diagnosis of malignant lesions were 66.67% and 57.50%, and the positive predictive value was 73.85%. The sensitivity and specificity of heterogeneity to the diagnosis of malignant lesions were 65.28% and 72.50%, and the positive predictive value was 81.03%. The combination of heterogeneous and absence of a linear‐discrete air bronchogram could improve the diagnostic specificity to 87.50%, and the positive predictive value to 80.77%. Conclusion The two EBUS echo features of heterogeneous and absence of a linear‐discrete air bronchogram have predictive value for PPLs, especially in the presence of two features the pulmonary lesions should be highly suspected malignant tumors.

Abstract Ulcerative colitis (UC) is a complicated and recurrent intestinal disease. Currently available drugs for UC treatment are scarce, therefore, novel therapeutic drugs for the UC are urgently to be developed. Gingerenone A (GA) is a phenolic compound known for its anti‐inflammatory effect, but its effect on UC remains unknown. Here, it is shown that GA protects mice against UC, which is closely associated with inhibiting intestinal mucosal inflammation and enhancing intestinal barrier integrity in vivo and in vitro. Of note, RNA sequencing analysis demonstrates an evident correlation with IL‐17 signaling pathway after GA treatment, and this effect is further corroborated by Western blot. Mechanistically, GA directly interacts with IL‐17RA protein through pull‐down, surface plasmon resonance analysis and molecular dynamics simulation. Importantly, lentivirus‐mediated IL‐17RA/Act1 knock‐down or GA co‐treatment with brodalumab/ixekizumab significantly impairs the protective effects of GA against DSS‐induced inflammation and barrier dysfunction, suggesting a critical role of IL‐17RA signaling for GA‐mediated protection against UC. Overall, these results indicate that GA is an effective agent against UC mainly through the direct binding of IL‐17RA to inhibit inflammatory signaling activation.

Abstract Despite the crucial role of the Southern Hemisphere (SH) westerlies in modulating modern and past climate evolution, little is known about their behavior and possible forcing mechanisms during the early Cenozoic. We probe changes in the hydroclimate of southwest Australia during 62–51 Ma, based on sedimentary proxy records from the International Ocean Discovery Program Site U1514 in the Mentelle Basin. Our results reveal a transition from a less humid climate to wetter conditions at mid–high latitudes starting from the early Eocene, which suggests poleward migration of the SH westerlies. This long‐term trend is punctuated by short‐lived events of aridification during the Mid‐Paleocene Biotic Event and wetter intervals during the Paleocene‐Eocene Thermal Maximum, indicating additional short‐term meridional shifting of the westerlies. We propose that the evolution of SH westerlies was driven by the equator‐to‐pole temperature gradient regulated by global warming and ephemeral growth of the Antarctic ice sheet.

Abstract Background To date, carbohydrate antigen 19‐9 (CA19‐9) and carcinoembryonic antigen (CEA) have been widely used for the screening, diagnosis and prediction of biliary tract cancer (BTC) patients. However, few studies with large sample sizes of carbohydrate antigen 50 (CA50) were reported in BTC patients. Methods A total of 1121 patients from the Liver Cancer Clin‐Bio Databank of Anhui Hepatobiliary Surgery Union between January 2017 and December 2022 were included in this study (673 in the training cohort and 448 in the validation cohort): among them, 458 with BTC, 178 with hepatocellular carcinoma (HCC), 23 with combined hepatocellular‐cholangiocarcinoma, and 462 with nontumor patients. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were used to evaluate the diagnostic efficacy and clinical usefulness. Results ROC curves obtained by combining CA50, CA19‐9, and AFP showed that the AUC value of the diagnostic MODEL 1 was 0.885 (95% CI 0.856–0.885, specificity 70.3%, and sensitivity 84.0%) in the training cohort and 0.879 (0.841–0.917, 76.7%, and 84.3%) in the validation cohort. In addition, comparing iCCA and HCC (235 in the training cohort, 157 in the validation cohort), the AUC values of the diagnostic MODEL 2 were 0.893 (95% CI 0.853–0.933, specificity 96%, and sensitivity 68.6%) in the training cohort and 0.872 (95% CI 0.818–0.927, 94.2%, and 64.6%) in the validation cohort. Conclusion The model combining CA50, CA19‐9, and AFP not only has good diagnostic value for BTC but also has good diagnostic value for distinguishing iCCA and HCC.

Abstract Predicting flood event classes aids in the comprehensive investigation of flood behavior dynamics and supports flood early warning and emergency plan development. Existing studies have mainly focused on historical flood event classification and the prediction of flood hydrographs or certain metrics (e.g., magnitude and timing) but have not focused on predicting flood event classes. Our study proposes a new approach for predicting flood event classes based on the class membership functions of flood regime metrics and hydrological modeling. The approach is validated using 1446 unimpacted flood events in 68 headstream catchments widely distributed across China. The new approach performs well, with class hit rates of 68.3% ± 0.4% for all events; 65.8% ± 0.6%, 56.8% ± 0.9%, and 69.5% ± 0.9% for the small, moderate and high spike flood event classes, respectively; and 82.5% ± 1.2% and 75.4% ± 1.1% for the moderate and high dumpy flood event classes, respectively. Furthermore, it performs better in the basins of northern China than in those of southern China, particularly for the small spike flood event class in the Songliao and Yellow River Basins, with hit rates of 80.0% ± 3.2% and 78.8% ± 3.2%, respectively. Our results indicate that the new approach will help improve the prediction performance of flood events and their corresponding classes, and provide deep insights into the comprehensive dynamic patterns of flood events for early warning and control management.

Abstract Food‐derived extracellular vesicles (FEVs) are nanoscale membrane vesicles obtained from dietary materials such as breast milk, plants and probiotics. Distinct from other EVs, FEVs can survive the harsh degrading conditions in the gastrointestinal tract and reach the intestines. This unique feature allows FEVs to be promising prebiotics in health and oral nanomedicine for gut disorders, such as inflammatory bowel disease. Interestingly, therapeutic effects of FEVs have recently also been observed in non‐gastrointestinal diseases. However, the mechanisms remain unclear or even mysterious. It is speculated that orally administered FEVs could enter the bloodstream, reach remote organs, and thus exert therapeutic effects therein. However, emerging evidence suggests that the amount of FEVs reaching organs beyond the gastrointestinal tract is marginal and may be insufficient to account for the significant therapeutic effects achieved regarding diseases involving remote organs such as the liver. Thus, we herein propose that FEVs primarily act locally in the intestine by modulating intestinal microenvironments such as barrier integrity and microbiota, thereby eliciting therapeutic impact remotely on the liver in non‐gastrointestinal diseases via the gut‐liver axis. Likewise, drugs delivered to the gastrointestinal system through FEVs may act via the gut‐liver axis. As the liver is the main metabolic hub, the intestinal microenvironment may be implicated in other metabolic diseases. In fact, many patients with non‐alcoholic fatty liver disease, obesity, diabetes and cardiovascular disease suffer from a leaky gut and dysbiosis. In this review, we provide an overview of the recent progress in FEVs and discuss their biomedical applications as therapeutic agents and drug delivery systems, highlighting the pivotal role of the gut‐liver axis in the mechanisms of action of FEVs for the treatment of gut disorders and metabolic diseases.

Background Metabolomics studies have identified various metabolic markers associated with stroke risk, yet much uncertainty persists regarding heterogeneity in these associations between different stroke subtypes. We aimed to examine metabolic profiles associated with incident stroke and its subtypes in Chinese adults. Methods and Results We performed a nested case–control study within the Dongfeng‐Tongji cohort, including 1029 and 266 incident cases of ischemic stroke (IS) and hemorrhagic stroke (HS), respectively, with a mean follow‐up period of 6.1±2.3 years. Fifty‐five metabolites in fasting plasma were measured by ultra‐high‐performance liquid chromatography–mass spectrometry. We examined the associations of metabolites with the risks of total stroke, IS, and HS, with a focus on the comparison of associations of plasma metabolite with IS and HS, using conditional logistic regression. We found that increased levels of asymmetrical/symmetrical dimethylarginine and glutamate were significantly associated with elevated risk of total stroke (odds ratios and 95%, 1.20 [1.08–1.34] and 1.22 [1.09–1.36], respectively; both Benjamini‐Hochberg‐adjusted P

Abstract Background Ion channels play an important role in tumorigenesis and progression of cervical cancer. Multiple long non‐coding RNA genes are widely involved in ion channel‐related signaling regulation. However, the association and potential clinical application of lncRNAs in the prognosis of cervical cancer are still poorly explored. Methods Thirteen patients with cervical cancer were enrolled in current study. Whole transcriptome (involving both mRNAs and lncRNAs) sequencing was performed on fresh tumor and adjacent normal tissues that were surgically resected from patients. A comprehensive cervical cancer‐specific lncRNA landscape was obtained by our custom pipeline. Then, a prognostic scoring model of ion‐channel‐related lncRNAs was established by regression algorithms. The performance of the predictive model as well as its association with the clinical characteristics and tumor microenvironment (TME) status were further evaluated. Results To comprehensively identify cervical cancer‐specific lncRNAs, we sequenced 26 samples of cervical cancer patients and integrated the transcriptomic results. We built a custom analysis pipeline to improve the accuracy of lncRNA identification and functional annotation and obtained 18,482 novel lncRNAs in cervical cancer. Then, 159 ion channel‐ and tumorigenesis‐related (ICTR‐) lncRNAs were identified. Based on nine ICTR‐lncRNAs, we also established a prognostic scoring model and validated its accuracy and robustness in assessing the prognosis of patients with cervical cancer. Besides, the TME was characterized, and we found that B cells, activated CD8+ T, and tertiary lymphoid structures were significantly associated with ICTR‐lncRNAs signature scores. Conclusion We provided a thorough landscape of cervical cancer‐specific lncRNAs. Through integrative analyses, we identified ion‐channel‐related lncRNAs and established a predictive model for assessing the prognosis of patients with cervical cancer. Meanwhile, we characterized its association with TME status. This study improved our knowledge of the prominent roles of lncRNAs in regulating ion channel in cervical cancer.

Abstract To improve the speed of mass transfer, a magnetic suspension platform (MSP) is used to transport the display chips. A novel 6‐DOF MSP is proposed in this paper. An improved Halbach array is used to supply the magnetic flux density. Two types of permanent magnets are utilised in the improved Halbach array. The smaller permanent magnet serves to consolidate the magnetic flux density, thereby enhancing the uniformity of the magnetic field. The finite element method is employed to analyse how variations in angle impact both the strength and uniformity of the magnetic flux density. The results show that the magnetisation direction of 45° is the most effective in terms of improving the uniformity and strength of the magnetic density. Finally, a 6‐DOF MSP prototype is manufactured. A magnetic density measurement experiment and a stable suspension experiment for the actuator are conducted. The results indicate an enhancement in the uniformity of the magnetic field within the air gap. Additionally, the maximum suspension positioning accuracy of the actuator is about 750 nm.